NGS influences treatment selection in AML

Roshini Claire Anthony
28 Jun 2018

The use of next generation sequencing (NGS) helps guide choice of treatment in more than 30 percent of patients with acute myeloid leukaemia (AML), according to findings from a single-centre study in the US.

“We believe that implementation of NGS is very feasible in AML, especially with such short reporting time of results [median time to results, 9 days],” said study lead author Dr Rita Elias Assi from the University of Texas MD Anderson Cancer Center in Houston, Texas, US.

“NGS guided targeted therapy in more than 30 percent of patients and that resulted in an increased proportion of patients treated with targeted therapy over 4 years, increased clinical trial accrual, but most importantly, increased response rates [with] potential positive effects on [relapse-free survival (RFS)],” she said.

This retrospective study conducted at the University of Texas MD Anderson Cancer Center between October 2012 and May 2016 included 1,470 adult patients (median age 63 years, 53 percent male) with AML (38 and 37 percent with newly diagnosed and relapsed/refractory AML, respectively). Bone marrow samples of the patients were submitted for NGS using either a 53- or 28-gene panel.

Researchers identified actionable mutations, defined as gene alterations that could be targeted with FDA-approved or investigational treatment agents either directly or through a nearby pathway; 17 genes that fit the criteria were selected (ALK, CSF1R, FGFR1, FGFR2, FGFR3, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, NRAS, NPM1, PDGFRA, PTPN11, RET, and TP53).

Median time between NGS testing and reporting of results was 9 days, with 80 percent of patients receiving their results within 2 weeks. [ASCO 2018, abstract 103]

Sixty-six percent of patients had at least one potentially actionable mutation with a median of two actionable mutations per patient, while 21 percent had no detectable mutations.

Eighty-six percent of patients (n=1,271) initiated therapy of whom 41 percent had been newly diagnosed with AML while 36 percent had relapsed/refractory AML. Sixty-five percent of patients (n=825) were enrolled in clinical trials, which were mostly phase I or II trials.

Over the 4-year study period, the rate of genomic matching to targeted therapy significantly increased, from 9 percent to 23 percent (p=0.001).

“This observation likely reflects the increased use of NGS testing and the increased awareness among patients and physicians to the presence of such strategies, as well as increased availability of biomarker-driven trials,” said Assi. 

Looking at patients who were treated in genotype-matched vs genotype unmatched trials, the overall response rates were higher among patients who received targeted therapy compared with those who did not regardless of whether they had newly diagnosed AML (72 percent vs 63 percent; p=0.04) or relapsed/refractory AML (31 percent vs 21 percent; p=0.001).

Patients with relapsed/refractory AML who received targeted therapy based on actionable mutations had improved RFS compared with those who did not receive targeted therapy (median, 7 vs 3.7 months; p=0.03), while there was a trend towards improved RFS among patients with newly diagnosed AML who received targeted therapy compared with those who did not (median, 21.5 vs 14.1 months; p=0.09).

The researchers acknowledged that the retrospective and single-centre design of the trial were limitations and looked forward to comparing the findings with results from other institutions.

“AML is a clinically and biologically heterogenous disease that continues to impose many clinical challenges and unmet needs. The advent of NGS has changed lots of things and has discovered many recurrent somatic mutations important for diagnosis, prognostication, and therapy selection in this setting,” said Assi. With the recent approval of new targeted therapies, we were interested to see how NGS may affect management of AML, she said. 

“We found that 66 percent of our patients harboured some actionable mutations and that opens the door for broader targeting especially in the era of precision medicine,” said Assi.


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